| Background:It is widely accepted that myasthenia gravis (MG),a T-cell-dependent chronic autoimmune disorder, is induced by sustained production of an antibody to the nicotinic acetylcholine receptors (AChR) at the neuromuscular-junction. MG is characterized by weakness and fatigability of skeletal, bulbar and extrocular muscles. It is reported that the development of MG is correlated with genetic, endocrine, environment and immune factors.None of those factors mentioned above, however, could explain the development of MG perfectly. Clinical evidence and experimental data suggest that MG is an autoimmune disease, in which polygenic inheritance and suspect genes play an important role. Numerous studies show that different autoimmune diseases may have common genetic factors, and susceptibility genes of an autoimme disease may be related to other autoimmune diseases. Single nucleotide polymorphism (SNP) is the most common genetic polymorphism of the human genome, used to study association with complex diseases. Moreover, the SNP in different ethnic origin and disease susceptibility may have different results. In this study we secleted 9 candidate SNPs associated with the susceptibility of several autoimmune diseases in Japanese such as rheumatoid arthritis and systemic lupus erythematosus, trying to explore the relevance of these gene polymorphisms with MG.Objective:The polymorphism of FCRL3 rs7528684, CD244 rs6682654, SLC22A4 rs2073838,RUNX1 rs2268277, STAT4 rs7574865, TRAF1 rs3761847, C5 rs10818488,BLK rs13277113 and IRF5 rs2004640 were analyzied. We investigated the association of these SNPs with the Japanese myasthenia gravis (MG) for early genetic diagnosis and early detecting high-risk groups, to provide the basis for the treatment of MGMethods:The study group comprised 52 patients with MG who were recruited from the Tokyo Womens Medical University. DNA was extracted from peripheral blood leucocytes according to standard methods.Genotyping was performed using ABI stepone real-time quantitative PCR instrument and taqman SNP genotyping kits fluorescent probes.We genotyped the above SNPs. The healthy controls in previous literatures studying the association between the SNPs and Japanese autoimmune diseases were also included. The chi-squared test was used to test the Hardy-Weinberg equilibrium. The chi-squared test was also performed to compare allelic frequencies of each SNP between cases and controls.The Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were calculated.Results:1.As previously seen for other autoimmune diseases, a significant difference was observed in the distribution of IRF5 rs2004640 between MG patients and healthy controls(T vs G:χ2=12.552,P<0.001,OR=2.071,95%CI[1.375-3.118];TT vs TG+GG:χ2=15.641,P<0.001,OR=3.719,95%CI[1.868-7.400]).It's showed that IRF5 rs2004640 is associated with the susceptibility of Japanese myasthenia gravis.2.FCRL3 rs7528684 was not associated with the risk of MG (C vs T:x2=0.508, P=0.476,OR=0.861,95%CI[0.570-1.300]).3.CD244 rs6682654 was not associated with the risk of MG (T vs C:χ2=0.225, P=0.635,OR=0.908,95%CI[0.608-1.356]).4.SLC22A4 rs2073838 was not associated with the risk of MG (A vs G:χ2=0.177, P=0.674,OR=1.093,95%CI[0.723-1.652]).5.RUNX1 rs2268277 was not associated with the risk of MG (C vs G:χ2=0.088, P=0.767,OR=1.064,95%CI[0.706-1.605]).6.STAT4 rs7574865 was not associated with the risk of MG (T vs G:χ2=0.048, P).826,OR=1.048,95%CI[0.692-1.586]).7.TRAF1 rs3761847 was not associated with the risk of MG (A vs G:χ2=0.158, P=0.691,OR=1.082,95%CI[0.734-1.595]).8.C5 rs10818488 G was not associated with the risk of MG (G vs A:χ2=0.592, P=0.442,OR=1.164,95%CI[0.790-1.716]).9.BLK rs13277113 was not associated with the risk of MG (G vs A:χ2=0.649, P=0.421,OR=1.182,95% CI[0.786-1.777]).Conclusions:The StepOneTM Real-Time PCR System delivers remarkable plug-and-play convenience and uncompromising performance. This factory-calibrated system makes it easy to step up to high performance real-time PCR. It's the first time to detect the association between the SNPs of FCRL3 rs7528684, CD244 rs6682654, SLC22A4 rs2073838,RUNX1 rs2268277,STAT4 rs7574865,TRAFl rs3761847,C5 rs10818488,BLK rsl3277113,IRF5 rs2004640 and the susceptibility to MG. An increased susceptibility associated to the IRF5 rs2004640 was found when MG patients and controls were compared. Our results at least comformed the relationship between this SNP and Japanese MG, provided a possible way to use IRF5 as a target in the treatment of MG and therefore extend the evidence of IRF5's general influence on autoimmunity. While the other 8 SNPs didn't show any association with MG. However, large, population-based studies are still necessary to confirm these findings. |
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